1. Update on Quality Pneumonia Care
Tosha Wetterneck, MD
Primary Care Conference
August 18, 2004

2. I do not have any financial disclosures or conflicts of interest to disclose.

3. Are physicians aware of and using pneumonia guidelines?
Answer: We can do better
Switzer, et al. JGIM 2003
Surveyed 621 MD’s at 7 hospitals in PA (response rate 56%)
>70% familiar with guidelines (ATS/local)
30-60% of those reported using guideline
Guidelines / Critical pathways for pneumonia can decrease LOS, cost and mortality*
*Marrie, JAMA 2000; Dean, Am J Med 2001

4. Objectives
Raise awareness of Community Acquired Pneumonia (CAP) guidelines
Review quality care for Community Acquired Pneumonia (CAP)
Understand the latest in CAP care
Antibiotic Selection
Diagnostic testing
Prevention
Learn about CAP Quality Initiatives at UWHC

5. Conclusions
CAP care is an important, publicly reported quality indicator
JCAHO and others monitor:
Blood Culture Use (prior to antibiotics)
Antibiotic Timing (within 4 hours of arrival)
Antibiotic Selection (new)
Smoking Cessation Counseling
Pneumococcal Screening & Vaccination
Influenza Screening & Vaccination (new)

6. Conclusions 2
Use UWHC guidelines for antibiotic selection (based on 2003 IDSA guidelines)
Use patient setting, comorbidities, allergies and recent antibiotic use to guide selection
Outpatient:
Healthy: macrolide or doxycycline
Comorbidities: Resp fluoroquinolone (FQ) or Ketolide or Macrolide + Beta-lactam
Inpatient:
Non ICU: Cephalosporin + Macrolide or Resp FQ
ICU: must use 2 drugs, assess for pseudomonas risk

7. Conclusions 3 Drug resistant pneumococcus is a growing problem
Nursing home:
Advanced macrolide + amox-clavulanate or Respiratory fluoroquinolone or Ketolide
Recent antibiotic therapy (3 months) confers risk for resistance and a different antibiotic class should be chosen
Drug resistant pneumococcus is a growing problem
Save the fluoroquinolones (judicious use)

8. Conclusions 4
Be aware of new antibiotics (ketolides), drug interactions and short course therapy
An ounce of prevention…
Patient Immunization: pneumococcal and influenza
Health Care Worker Influenza immunization
Smoking cessation counseling

9. Pneumonia is a growing health problem
4-5 million cases of CAP yearly
1.7 million hospitalizations annually
30-40 admissions per month at UWHC
7th leading cause of death in US
$10 billion dollars spent yearly on CAP
Inpatient: $5700/case, Outpatient: $300
$100 million on antimicrobials
National Vital Statistics Reports, 2001 data; AHRQ Research in Action #7

10. Gaps exist in quality of care
JCAHO Performance Measures
Agenda for Change, 1987
Core Measures
Developed ; Piloted 2001, 16 hospitals
Evidence-based quality indicators
Variety of stakeholders involved
Four Core Measures Sets selected (CAP, CHF, AMI, L&D)
Data collection at UWHC since 3rd Q 2003

11. 7 CAP Quality Indicators
Oxygenation assessment
Blood Culture Use (prior to antibiotics)
Antibiotic Timing (within 4 hours of arrival)
Antibiotic Selection (new)
Smoking Cessation Counseling
Pneumococcal Screening & Vaccination
Influenza Screening & Vaccination (new)

12. Quality Indicators and Outcomes
Early antibiotic therapy: decreased LOS and mortality
Blood cultures in first 24 hours: decreased mortality
Appropriate antibiotics: decreased LOS and mortality
Early IV to po antibiotic switch: decreased LOS and cost
Influenza vaccination: decreased mortality
Meehan, JAMA 1997; Battleman, Arch Int Med 2002; Gleason, Arch Int Med 1999; Ramirez, Arch Int Med 1999

13. CAP - Oxygen Assessment
Source: University HealthSystem Consortium JCAHO Core Measures, CY2003Q2, CY2003Q3, CY2003Q4, CY2004Q1

14. CAP – Blood Cultures (prior to Antibiotics)
Source: University HealthSystem Consortium JCAHO Core Measures, CY2003Q2, CY2003Q3, CY2003Q4, CY2004Q1

15. CAP - Antibiotic Timing, mean time

16. CAP - Antibiotic Timing, median time

17. CAP - Smoking Cessation Counseling

18. CAP - Pneumococcal Screening/Vaccine

19. Everyone wants this data…
CMS voluntary reporting (2003)
Public data released Feb 04
Tied to reimbursement
JCAHO public data reporting (July 2004)
WHA public reporting (March 2004)
WI Collaborative for Healthcare Quality
UWHC Quality and Safety Report
Business report: July 2004
Consumer report: Sept 2004

20. Remainder of talk… Understand the latest in CAP care
Antibiotic Selection
Diagnostic testing
Prevention
Learn about CAP Quality Initiatives at UWHC

21. Etiology of CAP Causative agent known in less than half of patients
Bacterial: 40-60%,
S pneumoniae (15-35%), H flu, Moraxella
Atypical pathogens: 10-30%
Mycoplasma, Chlamydia, Legionella
Other agents: 5%-25%
Viruses, PCP, MTB
Unknown: 30-60%, two agents: 15%

22. IDSA 2003 Guidelines Latest guidelines for CAP treatment
Update 2000 guidelines
UWHC guidelines based heavily on IDSA guidelines + latest evidence

23. Antibiotic selection guidelines
Setting:
Outpatient vs. Inpatient, non-ICU vs ICU
Patient factors:
Comorbidities: COPD, diabetes, renal disease, CHF or malignancy
Recent antibiotic therapy: within past 3 months= choose different antibiotic class
Pseudomonal risk: severe structural lung disease, recent Abx or stay in hospital

24. Please forgive my use of unapproved abbreviations in the remainder of the talk
q = every
b.i.d. = twice daily
t.i.d. = three times daily
q.i.d. = four times daily

25. * Patients usually young, non-smoking
Outpatient treatment- Previously healthy patient, no recent antimicrobial therapy*
Preferred treatment:
Macrolide or doxycycline
Specific antimicrobial choices:
Azithromycin, one Z pak as directed OR Clarithromycin 500mg b.i.d. x 10 days OR Erythromycin for days
Doxycycline 100mg b.i.d. x days
* Patients usually young, non-smoking

26. Outpatient treatment- Previously healthy patient, +recent antimicrobial therapy*
Preferred treatment:
Advanced macrolide + high dose amoxicillin
Advanced macrolide + amox-clavulanate
Respiratory fluoroquinolone
Ketolide
* Risk factor for resistant pneumococcus

27. * Augmentin XR is 1000mg amoxicillin and 125mg clavulanate
Outpatient treatment- Previously healthy patient, +recent antimicrobial therapy
Specific antimicrobial choices:
Azithromycin, one Z pak as directed OR Clarithromycin 500mg b.i.d. x 10 days + Amoxicillin 1g t.i.d. OR Amoxicillin-clavulanate XR* 2 tablets b.i.d. x 10 days
Moxifloxacin 400mg daily x 10 days OR Gatifloxacin 400mg daily x 10 days OR Levofloxacin 750mg daily x 5 days
Telithromycin 800mg daily x 7-10 days
* Augmentin XR is 1000mg amoxicillin and 125mg clavulanate

28. Outpatient treatment- Comorbidities*, no recent antimicrobial therapy
Preferred treatment:
Advanced macrolide
Respiratory fluoroquinolone
Ketolide
*COPD, diabetes, renal disease, CHF or malignancy

29. Outpatient treatment- Comorbidities, No recent antimicrobial therapy
Specific antimicrobial choices:
Azithromycin, one Z pak as directed OR Clarithromycin 500mg b.i.d. x 10 days
Moxifloxacin 400mg daily x 10 days OR Gatifloxacin 400mg daily x 10 days OR Levofloxacin 750mg daily x 5 days
Telithromycin 800mg daily x 7-10 days

30. Outpatient treatment- Comorbidities, +Recent antimicrobial therapy
Preferred treatment:
Advanced macrolide + beta-lactam
Respiratory fluoroquinolone
Ketolide

31. Outpatient treatment- Comorbidities, +Recent antimicrobial therapy
Specific antimicrobial choices:
Azithromycin, one Z pak as directed OR Clarithromycin 500mg b.i.d. x 10 days + Amoxicillin 1g t.i.d. x OR Amoxicillin-clavulanate XR* 2 tablets b.i.d. OR Cefpodoxime 200mg b.i.d. x 10 days
Moxifloxacin 400mg daily x 10 days OR Gatifloxacin 400mg daily x 10 days OR Levofloxacin 750mg daily x 5 days
Telithromycin 800mg daily x 7-10 days
* Augmentin XR is 1000mg amoxicillin and 125mg clavulanate

32. Outpatient treatment- Suspected aspiration
Preferred treatment:
Amoxicillin-clavulanate or Clindamycin
Specific antimicrobial choices:
Amoxicillin-clavulanate 875/125mg b.i.d. x 10 days
Clindamycin 300mg q.i.d. x 10 days

33. Outpatient treatment- Influenza with bacterial superinfection
Preferred treatment:
Beta-lactam
Respiratory Fluoroquinolone

34. Outpatient treatment- Influenza with bacterial superinfection
Specific antimicrobial choices:
Amoxicillin 1 g t.i.d. OR Amoxicillin-clavulanate XR* 2 tablets b.i.d. OR Cefpodoxime 200mg b.i.d. x 10 days
Moxifloxacin 400mg daily x 10 days OR Gatifloxacin 400mg daily x 10 days OR Levofloxacin 750mg daily x 5 days
* Augmentin XR is 1000mg amoxicillin and 125mg clavulanate and may not be on all formularies

35. Inpatient treatment- Non-ICU, No recent antimicrobial therapy
Preferred treatment:
Advanced macrolide + beta-lactam
Respiratory fluoroquinolone
Specific antimicrobial choices:
Ceftriaxone 1 g IV daily + Azithromycin 500 mg IV daily
Moxifloxacin 400mg IV daily

36. Inpatient treatment- Non-ICU, +Recent antimicrobial therapy
Preferred treatment:
Sane as above EXCEPT choose a different antibiotic than previous therapy
Specific antimicrobial choices:
Ceftriaxone 1 g IV daily + Azithromycin 500 mg IV daily
Moxifloxacin 400mg IV daily

37. Inpatient treatment- ICU, No pseudomonal risk*
Preferred treatment:
Beta-lactam + Advanced macrolide OR Respiratory fluoroquinolone
Specific antimicrobial choices:
Ceftriaxone 1 g IV daily + Azithromycin 500 mg IV daily OR Moxifloxacin 400mg IV daily
*Pseudomonal risk: severe structural lung disease, recent Abx or stay in hospital

38. Inpatient treatment- ICU, No pseudomonal risk, +Beta lactam allergy
Preferred treatment:
Respiratory fluoroquinolone +/- Clindamycin
Specific antimicrobial choices:
Moxifloxacin 400mg IV daily +/- Clindamycin mg IV every 6 hours

39. Inpatient treatment- ICU, +Pseudomonal risk*
Preferred treatment:
Antipseudomonal agent + Ciprofloxacin
Antipseudomonal agent + Aminoglycoside + Respiratory fluoroquinolone OR Advanced macrolide
*Pseudomonal risk: severe structural lung disease, recent Abx or stay in hospital

40. Inpatient treatment- ICU, +Pseudomonal risk
Specific antimicrobial choices:
Piperacillin 4g IV q6h OR Piperacillin-tazobactam 4.5g IV q6h OR Cefepime 2g IV q8h OR Imipenem 500mg q6h + Ciprofloxacin 400mg IV q8h
Piperacillin 4g IV q6h OR Piperacillin-tazobactam 4.5g IV q6h OR Cefepime 2g IV q8h OR Imipenem 500mg q6h + Gentamicin OR Tobramycin OR Amikacin + Moxifloxacin 400mg IV daily OR Azithromycin 500 mg IV daily

41. Inpatient treatment- ICU, +Pseudomonal risk +Beta-lactam allergy
Preferred treatment:
Aztreonam + Antipseudomonal agent +/- Aminoglycoside
Specific antimicrobial choices:
Aztreonam 2g q8h + Ciprofloxacin 400mg IV q8h OR Levofloxacin 750mg IV daily +/- Gentamicin OR Tobramycin OR Amikacin

42. Nursing Home Treatment
Preferred treatment:
Advanced macrolide + amox-clavulanate
Respiratory fluoroquinolone
Ketolide

43. Nursing Home Treatment
Specific antimicrobial choices:
Azithromycin, one Z pak as directed OR Clarithromycin 500mg b.i.d. x 10 days + Amoxicillin-clavulanate XR 2 tablets b.i.d. x 10 days
Moxifloxacin 400mg daily x 10 days OR Gatifloxacin 400mg daily x 10 days OR Levofloxacin 750mg daily x 5 days
Telithromycin 800mg daily x 7-10 days

44. Caveats to Antibiotic Therapy
Drug resistant pneumococci
Monotherapy vs. dual therapy
Fluoroquinolone therapy
Ketolides
QT prolongation side effects
Short course therapy

45. S. Pneumoniae : Growing Antimicrobial resistance in US
PCN resistance growing
39% of US isolates have high or intermediate level resistance
3-4% increase yearly from 1995
¾ PCN resistant also macrolide resistant
Erythromycin resistance: 31%
Cefuroxime resistance: 30%
Fluoroquinolone resistance: 1%
Doern, J Inf 2004

46. Drug Resistant Pneumococci
Risk Factors:
Age > 65
Beta-lactam therapy last 3 months*
Alcoholism
Immunosuppression (including steroids)*
Exposure to child in day care
Multiple comorbidities*
*Shown in multiple studies
Ewig, J Respir Crit Care Med 1999

47. Clinical Impact of Pneumococcal Resistance in CAP patients
Aspa, et al. CID 2004
Prospective, multi-center obs study of 638 patients with CAP due to S pneumo in Spain
Isolates: 10% PCN-R, 26% PCN-I
Morbidity: DIC, empyema & bacteremia more common with PCN-S isolates
Mortality: 18% (PCN-R) vs. 18% (PCN-I) vs. 12% (PCN-S), p=.054 (underpowered)
Song, et al. CID Asia, 233 patients.
No difference in mortality but underpowered

48. Clinical Impact of Pneumococcal Resistance in Bacteremic patients
Yu, et al. CID 2003
Prospective, international, multi-center study of 844 bacteremic patients
PCN resistance: 9.6%; 14 d mortality rate 16.9%
Overall, persons with PCN resistant S. pneumo who received monotherapy with ‘the wrong’ antibiotic died at same rate as those who received ‘the right’ antibiotic
Exception: Cefuroxime (standard dosing does not achieve levels above MIC)
65% deaths occurred w/i 3 days of BCx

49. Macrolide Resistant Pneumococci
Mechanisms of resistance:
Efflux pump
Ribosomal alteration- prevents macrolide binding to ribosome
Macrolide failures in CAP caused by S. pneumo resistance
Associated with breakthrough bacteremia
Not recommended as monotherapy in bacteremic patients
Lonks, CID 2002

50. Fluoroquinolone resistant pneumococcus
In US: resistance to FQ low but reported
In Canada and Spain: resistance with FQ use
Likelihood of FQ resistance increases with prior FQ exposure in past year
Reports of patients on FQ who have FQ resistant pneumococcus show increased morbidity and mortality
Resistance may develop during treatment
Some guidelines recommend FQ as first line agent due to low resistance rates
Chen, NEJM 1999

51. Fluoroquinolone Recommendations
Fluoroquinolones have established efficacy in CAP treatment
Serious CAP, S. pneumo bacteremia, Macrolide & PCN resistant S. pneumo
Most experts and IDSA guidelines recommend restricted use over concern of increased resistance
Patients who fail or are allergic to beta lactam + macrolide therapy
Documented highly drug resistant pneumococcus
File, CID 2004

52. Take home points – Drug Resistant Pneumococci
Rates of drug resistant pneumococcus are increasing
Clear reports of macrolide and fluoroquinolone resistant strains causing morbidity and mortality in patients receiving those antibiotics
PCN resistance so far does not seem to cause worse outcomes…more evidence is needed
Can be overcome with higher doses of drug
Fluoroquinolones are a last resort

53. Monotherapy vs. Dual therapy
Guidelines for antibiotics in hospitalized patients:
Non-ICU: Macrolide addition to beta-lactam/cephalosporin or fluoroquinolone alone; some macrolide alone
ICU: 2 drugs: FQ or macrolide + beta-lactam/inh or ceph
Multiple retrospective and prospective observational studies have shown decreased LOS a/o mortality with dual therapy with macrolide addition vs. cephalosporin or augmentin alone
Fluoroquinolone monotherapy also with lower mortality
Macrolide monotherapy studies mixed
Martinez, CID 2004

54. Monotherapy vs. Dual therapy
Quasi RCTs examining monotherapy vs. dual therapy show no difference
Limited due to small ‘n’, non-blinded medication assignment
Data for fluoroquinolone monotherapy more convincing
Fogarty, et al. CID 2004
Randomized, non-blinded study of 269 patients with serious CAP to show Abx equivalence
Initial Rx: Levofloxacin vs. Ceftriaxone + erythromycin
No difference in clinical response, mortality
Similar findings seen in 5 other studies of FQs

55. 2 studies support dual therapy in S pneumo bacteremia
Waterer, Arch Int Med 2001
Retrospective study of 255 patients with S. pneumo bacteremia, outcome=14 day mortality
Monotherapy associated with death (even FQ)
Dual therapy with ceph + macrolide or FQ best outcomes
Martinez, CID 2003
Observational study of 409 patients with S. pneumo bacteremia who received initial beta-lactam therapy, outcome=in hospital mortality
1/3 also received macrolide therapy
Lack of initial macrolide therapy associated with death
FQ not studied

56. Why might dual therapy work better?
Macrolide or FQ addition thought to cover atypical bacteria co-infection
Macrolides have immunomodulatory effects
Benefit seen in bronchiolitis and cystic fibrosis
Not a proven mechanism in CAP
Doesn’t explain similar results with FQ addition in Waterer study
Studies based on initial empiric antibiotics, not focused S pneumo therapy
Martinez, CID 2004

57. How do you know who could be bacteremic?
Initial antibiotic choice made before blood culture results known
High risk patients for bacteremia:
≥65 years old
Asplenic or immunocompromised
High risk for complications from bacteremia:
Above + Comorbid disease: CV, lung, liver, diabetes
Bacteremia is a risk factor for death

58. Monotherapy vs. Dual therapy Conclusions
In hospitalized patients, cephalosporins and beta-lactamase inh should not be used as single therapy
Macrolide monotherapy should be reserved for young, non-ill / immunocompromised / bacteremic patients
Use 2 drugs in ICU patients: beta lactam + macrolide or FQ

59. Ackermann, J Antimicr Chemo 2003
Ketolides
Semi-synthetic derivative of erythromycin designed to overcome macrolide resistant S. pneumo
Binds to 2 subunits on ribosome, weak inducer of efflux pump
Used in Europe since 2001, FDA approved April 2004
Expect to see marketing soon
Ackermann, J Antimicr Chemo 2003

60. Ketolides 2
3 RCTs document equivalence with amoxicillin, clarithromycin and quinolones
Role in macrolide-resistant S pneumo: No resistance seen yet
No firm data in patients with S. pneumo bacteremia

61. Ackermann, J Antimicr Chemo 2003
Ketolides 3
Dosing: 800 mg per day (p.o. only)
No change in renal / hepatic dysfxn
7-10 day course for pneumonia
ADRs: diarrhea (13%), nausea, h/a
Significant drug interactions:
Metabolized by CYP3A4 system : Do not use with Statins (hold statin), protease inhibitors (HIV), CSA, tacrolimus
Ackermann, J Antimicr Chemo 2003

62. CAP drugs with QT prolongation potential
Telithromycin
Moxifloxacin – moreso than levo, gati, cipro
Recommend use with caution if:
Known QT prolongation
Taking drugs that prolong the QT interval
Uncorrected hypokalemia

63. Short course antibiotic therapy
Proposed to decrease antimicrobial resistance, side effects & non-adherence
Hospitalized patients with CAP:
Levofloxacin 750mg daily x 5 days just as good as 500mg daily x 10 days
Outpatients with CAP:
Telithromycin 800mg daily for 5 days as good as 7 days
Azithromycin 500mg daily x 3 days as good as Clarithromycin 500mg twice daily x 10 days
File, CID 2004

64. Diagnostic testing on Hospitalized patients
2 v Chest X ray (confirm dx, effusion)
Blood cultures on arrival (before abx)
Sputum GS and culture (before abx)
Urine Legionella antigen- only patients with risk factors
Seriously ill
Immunocompromised
Non-responsive to beta-lactams
Suggestive clinical features

65. New diagnostic test: Pneumococcal Urinary Antigen
Detects pneumococcal cell wall polysaccharide in urine
Rapid turnaround: 15 min –1 hour
Sensitivity: 50-80%, specificity: 90%
70-80% in bacteremic patients
Should not replace cultures
Needed for susceptibility testing

66. New diagnostic test: Pneumococcal Urinary Antigen 2
Considered a “possibly useful addition” by IDSA panel
Helpful for patients already on antibiotics at the time of evaluation
High risk patients with non-diagnostic sputum
Should be available at UWHC later this year or early 2005

67. Back to the Quality piece……

68. CAP Quality efforts at UWHC
CAP guidelines on CRIT (updated 8/2004)
Includes PSI, antibiotic selection
Focused Efforts: PICC team for CAP
Time to First dose antibiotics
Inpatient Immunization Protocol – Pneumococcal and Influenza vaccines
Smoking Cessation counseling
Documentation standardization
Blood culture protocol update

69. Time to First dose antibiotics
Goal < 4 hours, door to drug time
How Physicians can help:
Treat 1st dose of antibiotics as “STAT”
Write for antibiotics on admission ASAP
Verbally communicate with Pharmacy and nursing
Be prepared to help ensure IV access
Attendings: encourage your residents!

70. Inpatient Immunization Protocol – Pneumococcal and Influenza vaccines
Hospitalized patients at UW will be screened by pharmacists and case managers for prior pneumococcal and influenza immunization based on ACIP guidelines
Eligible patients will receive vaccine at discharge by protocol (no physician order needed)
Immunization will be documented in WISCR and patient given vaccine card

71. Prevention of Pneumonia
Patient Immunization:
Influenza vaccine shown to:
Reduce hospitalization for cardiac disease and stroke in elderly
Reduce mortality in elderly
Pneumococcal vaccine:
Prevent invasive disease (bacteremia)
Reduce hospitalizations and death in elderly with chronic lung disease

72. Prevention of Pneumonia 2
Health Care Worker Influenza Immunization
Reduced absenteeism from work
Reduced patient and colleague morbidity and mortality from work transmission
Please vaccinate your patients and yourself!

73. Prevention of Pneumonia 3
Smoking Cessation Counseling
Need to document this for all inpatients with Pneumonia who:
Currently smoke
Smoked in the past year
Multidisciplinary team convening to implement this on the inpatient setting

74. Conclusions
CAP care is an important, publicly reported quality indicator
JCAHO and others monitor:
Oxygenation assessment
Blood Culture Use (prior to antibiotics)
Antibiotic Timing (within 4 hours of arrival)
Antibiotic Selection (new)
Smoking Cessation Counseling
Pneumococcal Screening & Vaccination
Influenza Screening & Vaccination (new)

75. Conclusions 2
Use UWHC guidelines for antibiotic selection (based on 2003 IDSA guidelines)
Use patient setting, comorbidities, allergies and recent antibiotic use to guide selection
Outpatient:
Healthy: macrolide or doxycycline
Comorbidities: Resp fluoroquinolone (FQ) or Ketolide or Macrolide + Beta-lactam
Inpatient:
Non ICU: Cephalosporin + Macrolide or Resp FQ
ICU: must use 2 drugs, assess for pseudomonas risk

76. Conclusions 3 Drug resistant pneumococcus is a growing problem
Nursing home:
Advanced macrolide + amox-clavulanate or Respiratory fluoroquinolone or Ketolide
Recent antibiotic therapy (3 months) confers risk for resistance and a different antibiotic class should be chosen
Drug resistant pneumococcus is a growing problem
Save the fluoroquinolones (judicious use)

77. Conclusions 4
Be aware of new antibiotics (ketolides), drug interactions and short course therapy
An ounce of prevention…
Patient Immunization: pneumococcal and influenza
Health Care Worker Influenza immunization
Smoking cessation counseling

78. Resources UWHC Pneumonia guidelines (CRIT) IDSA guidelines online
Pneumonia Bibliography